Speed of reversal by sugammadex or neostigmine after vecuronium-induced neuromuscular block in dogs: Randomized clinical trial and pharmacological modeling

Abstract

ObjectiveTo compare recovery times from vecuronium-induced neuromuscular block with sugammadex or neostigmine, and to estimate recovery times using simulated, clinically relevant scenarios, with nonlinear mixed-effect (NLME) models.Study designRandomized clinical trial and pharmacological modeling.AnimalsA group of 30 adult dogs of various breeds undergoing ophthalmic surgery.MethodsNeuromuscular block was induced and maintained with vecuronium. Train-of-four (TOF) count (n) or ratio (%) was quantified with acceleromyography every minute. Dogs were randomized to intravenous injection of sugammadex (4 or 1 mg kg–1) or neostigmine/atropine (0.04/0.02 mg kg–1) following surgery. Treatment effect on recovery time, time from last dose of vecuronium, and TOF and temperature at the time of reversal were assessed with a generalized linear model. NLME models were created and simulations of subpopulations (n = 7500) performed for reversal with each treatment at a TOF count 0–3 and performed between 0–20 or 21–50 minutes after vecuronium.ResultsReversal occurred at a TOF count or ratio of 1 (0–8)%, 1 (0–52)% and 2 (0–30)% for sugammadex 4 mg kg–1, 1 mg kg–1 and neostigmine, respectively. Treatment and time from last vecuronium significantly affected reversal time (both p ≤ 0.005; all treatments differed from one another). Recovery times were 2 (1–5), 3 (2–14) and 7.5 (5–19) minutes, respectively, and these findings were supported by NLME model simulations. A longer time between last administration of vecuronium and neostigmine reversal resulted in faster recovery. Recovery times up to 5, 13 and 30 minutes can be expected for these reversal regimes.Conclusions and clinical relevanceRecovery from vecuronium-induced neuromuscular block with sugammadex was dose dependent and faster than neostigmine. Substantial variation in recovery times is expected with low-dose sugammadex and neostigmine, highlighting the importance of monitoring.